| Protocol | In Vitro | In vitro activity: LGD‐3303 is a nonsteroidal, nonaromatizable androgen receptor ligand that binds to the androgen receptor with high affinity in a radiolabeled to competitive binding assay (Ki = 0.9 nM). LGD‐3303 binds to the mineralocorticoid, glucocorticoid, and progesterone receptors with greatly reduced affinity in comparison with the androgen receptor (Ki = 1261, 581, and 136 nM, respectively). LGD‐3303 potently activates transcription through the androgen receptor (EC50 = 3.6 nM) and has 134% efficacy relative to the steroidal androgen DHT. LGD‐3303 has minimal activity on other related nuclear hormone receptors in a transcriptional activity assay. Maximal efficacy relative to the natural ligands was determined to be 10% for the mineralocorticoid receptor, 1% for the glucocorticoid receptor, 1% for the estrogen receptor α, and 38% for the progesterone receptor. Potency could only be determined for the mineralocorticoid receptor (EC50 = 3695 nM) and the progesterone receptor (EC50 = 2233 nM). Kinase Assay: LGD‐3303 is a nonsteroidal, nonaromatizable androgen receptor ligand that binds to the androgen receptor with high affinity in a radiolabeled to competitive binding assay (Ki = 0.9 nM). LGD‐3303 binds to the mineralocorticoid, glucocorticoid, and progesterone receptors with greatly reduced affinity in comparison with the androgen receptor (Ki = 1261, 581, and 136 nM, respectively). LGD‐3303 potently activates transcription through the androgen receptor (EC50 = 3.6 nM) and has 134% efficacy relative to the steroidal androgen DHT. Cell Assay: Data were collected at 10 Hz from the load cell and the cross‐head displacement and analyzed using software designed for materials testing (TestWorks 4; MTS). Whole femurs were tested to failure in three‐point bending, and the fifth lumbar vertebral body was tested to failure in compression after removal of the endplates and spinous processes. The preparation and testing of the vertebral body have been previously described. Maximum load, stiffness, and energy absorption were measured from the load‐deformation curve for each specimen. Elastic modulus, maximum stress, and toughness were calculated based on standard engineering equations for three‐point bending or compression testing, respectively. |
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| In Vivo | Both testosterone propionate and LGD‐3303 had anabolic activity in muscle in ORDX male rats, significantly increasing the levator ani weight in a dose‐dependent manner. Histological examination was not performed in this experiment; however, examination of H&E‐stained skeletal muscle sections in other studies showed no abnormal histological findings at doses of LGD‐3303 up to 450 mg/kg, suggesting normal muscle physiology (unpublished data). LGD‐3303 and testosterone displayed similar potency, maintaining the levator ani near eugonadal levels with a 1‐mg/kg dose. Testosterone stimulated the ventral prostate to 50% of eugonadal levels with the 1‐mg/kg dose and exceeded the eugonadal level with the 3‐mg/kg dose, indicating minimal tissue selective activity. LGD‐3303, however, had negligible activity on the ventral prostate at 1 mg/kg (<5% efficacy). At higher doses of LGD‐3303, the ventral prostate weight never reached the eugonadal level, restoring the ventral prostate to <50% of eugonadal levels at 100 mg/kg. The finding that prostate weight is maximally stimulated by LGD‐3303 to a level markedly less than testosterone, a full agonist, indicates that this compound is a partial agonist on the prostate. This partial agonist activity on the prostate occurred despite increasing plasma concentrations of compound (data not shown). |
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| Animal model | ORDX male rats |
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These protocols are for reference only. InvivoChem does not
independently validate these methods.
Preparing Stock Solutions
| Solvent volume to be added |
Mass (the weight of a compound) |
| Mother liquor concentration |
1mg | 5mg | 10mg | 20mg |
| 1mM | 2.9176 mL | 14.5879 mL | 29.1758 mL | 58.3516 mL |
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| 5mM | 0.5835 mL | 2.9176 mL | 5.8352 mL | 11.6703 mL |
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| 10mM | 0.2918 mL | 1.4588 mL | 2.9176 mL | 5.8352 mL |
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| 20mM | 0.1459 mL | 0.7294 mL | 1.4588 mL | 2.9176 mL |
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Quality Control Documentation
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